Microorganisms possess a plethora of regulatory mechanisms to tightly control the flux through their metabolic network, allowing optimal behaviour in response to environmental conditions. However, these mechanisms typically counteract metabolic engineering efforts to rewire the metabolism with a view to overproduction. Hence, overcoming flux control is key in the development of microbial cell factories, illustrated in this contribution using the strictly controlled hexosamine biosynthesis pathway.

The hexosamine biosynthesis pathway has recently garnered attention as gateway for the industrial biotechnological production of numerous mono-, oligo- and polysaccharidic compounds, composed of, i.a., glucosamine, N-acetylglucosamine, and neuraminic acid and with a vast application potential in the health, comsetics, and agricultural sector. First, the various alternative pathways in eukaryotes and prokaryotes are discussed. Second, the main regulatory mechanisms on transcriptional, translational and post-translational control, and the strategies to circumvent these pathway bottlenecks are highlighted. These efforts can serve as an inspiration to tackle regulatory control when optimizing any microbial cell factory.

微生物拥有多种调控机制，可以通过其代谢网络严格控制通量，从而能够根据环境条件实现最佳行为。然而，这些机制通常抵消了代谢工程学以重新合成代谢以达到过度生产的努力。因此，克服通量控制是微生物细胞工厂发展的关键，这在使用严格控制的己糖胺生物合成途径的贡献中得到了说明。

己糖胺生物合成途径，最近获取了注意，因为网关用于工业生物技术生产大量的单- ，寡糖和多糖化合物，组成IA，葡萄糖，ñ乙酰氨基葡萄糖和神经氨酸，并与卫生广阔的应用前景，化妆品和农业领域。首先，讨论了真核生物和原核生物的各种替代途径。其次，重点介绍了转录，翻译和翻译后控制的主要调控机制，以及规避这些途径瓶颈的策略。这些努力可以作为在优化任何微生物细胞工厂时解决法规控制的灵感。